tbuckley/cabot-search huggingface dataset:
Abstract 13766: Delays in Care and Outcomes in Out-of-Hospital Cardiac Arrest With Shockable Rhythm
Authors: Kevin M Wheelock, Elliott Miller, Rohan Khera
Journal: Circulation (2022)

Introduction: Longer duration of ventricular fibrillation (VF) and pulseless ventricular tachycardia (pVT) is associated with worse outcomes among cardiac arrest patients. The ROC-ALPS trial randomized adults with shock-refractory VF or pVT to receive amiodarone, lidocaine, or placebo and found no difference in outcomes with either amiodarone or lidocaine. We sought to quantify the delay in drug administration and its effect on outcomes. Methods: We performed a retrospective analysis of the ROC-ALPS trial dataset. We included all patients who achieved return of spontaneous circulation (ROSC), had documented time to first shock, and time to trial drug administration. A logistic regression model was created with the time to drug administration after first shock, time to first shock, time to ROSC, study randomization arm, and other covariates, as a predictor of survival and neurologic disability (Modified Rankin Scale &gt;=4) at hospital discharge. Results: A total of 1439 patients (1116 male, mean age 63.5 [SD 13.9] years) were included, with 1043 (72.5%) of arrests witnessed. The median (IQR) time to first shock was 9.5 (7.8 - 11.6) minutes, and patients received a median of 4 (3 - 7) shocks. The median time from first shock to study drug administration was 6.9 (4.4 - 10.5) minutes. Three hundred and nine (21.5%) patients received the trial drug within 4 minutes of first shock, 540 (37.5%) had delay of 4 - 8 minutes, 309 (21.5%) had delay of 8 - 12 minutes, and 281 (19.5%) had delay of &gt; 12 minutes. Delay in trial drug administration of greater than 12 minutes from first shock was associated with worse survival and neurologic function at hospital discharge ( Table ). This effect was not modified by drug randomization group. Conclusion: Among out-of-hospital cardiac arrest patients with shock-refractory VF or pVT who achieved ROSC, there was an association between delayed medication administration, a measurable surrogate for overall delays in care, and worse outcomes.
Abstract 13254: Klotho Suppresses Endothelial-to-Mesenchymal Transition in the Aorta of Mice With Chronic Kidney Disease by Inhibition of Endothelial Senescent Activity
Authors: Qingzhou Yao, Erlinda The, Yufeng Zhai, Lihua Ao, David Fullerton, Xianzhong Meng
Journal: Circulation (2022)

Background: Klotho is an anti-aging protein expressed primarily in the kidney and vasculature. Chronic kidney disease (CKD) results in hyperphosphatemia. We reported that high levels of phosphate downregulate Klotho expression in vascular cells. Endothelial-to-mesenchymal transition (EndMT) in arteries promotes the development of atherosclerosis, and CKD is a significant risk factor for atherosclerosis. However, the impact of CKD on EndMT in arteries is unclear and whether Klotho insufficiency plays a role in the mechanism underlying vascular EndMT remains unknown. This study tested the hypothesis that Klotho insufficiency associated with CKD induces senescence in arterial endothelial cells to upregulate EndMT. Methods and Results: We developed a CKD model in C57/BL6 mice (5-6 months old) on AIN-76A diet and treated with adenine and calcitriol. CKD was confirmed by markedly elevated blood levels of creatinine and phosphate, as well as by renal tubular damage. En face immunofluorescence staining of aorta and image quantification revealed that the levels of biomarkers of senescence (P21) and EndMT (vimentin) were greater, while Klotho levels were lower, in the aortic arch endothelial cells of CKD mice compared to sham control mice. P21 and vimentin were co-localized in a greater number of endothelial cells in the aortic arch of CKD mice. High phosphate treatment upregulated the levels of P21 and vimentin and reduced the levels of Klotho in both primary human and mouse aortic endothelial cells, and knockdown P21 attenuated EndMT induced by high phosphate. Recombinant Klotho suppressed both senescence and EndMT in primary human aortic endothelial cells. Further, prolonged treatment of CKD mice with recombinant Klotho attenuated endothelial senescence and EndMT in the aortic arch. Conclusion: Klotho insufficiency associated with CKD promotes endothelial senescence and EndMT in aorta. High phosphate is capable of inducing endothelial senescent change that provokes EndMT. Administration of recombinant Klotho or upregulation of Klotho expression may have therapeutic potential for suppressing pro-atherosclerosis activity in large arteries by prevention of endothelial senescence and resultant EndMT.
Abstract 13864: Can Catheter Ablation Be Effective in Patients With Persistent Atrial Fibrillation and Heart Failure With Preserved Ejection Fraction Diagnosed Using HFA-PEFF Score?
Authors: Kosuke Nakasuka, Yukako Oishi, Yoshiro Tsuruta, Marina Ishida, Yu Kawada, Kento Mori, Shohei Kikuchi, Shuichi Kitada, Toshihiko Goto, Yoshihiro Seo
Journal: Circulation (2022)

Background: The efficiency of atrial fibrillation (AF) ablation for heart failure with preserved ejection fraction (EF) (HFpEF) has not been well investigated due to the difficulty of diagnosing HFpEF. The HFA-PEFF score from the European Society of Cardiology has been introduced as a new non-invasive diagnostic system for HFpEF. Methods: We studied 101 persistent AF patients with EF≥50% who underwent first catheter ablation (age 70±10 years, 68 men). The HFA-PEFF score was calculated as a sum of points in echocardiographic functional and morphological, and biomarker (brain natriuretic peptide: BNP) domains. Based on the HFA-PEFF score, patients were divided into High-group (score of ≥5, n=34) and Low-group (score of &lt;5, n=67). Results: The High-group had older, higher BNP levels, left atrial volume index (LAVI), and E/e' than those in the Low-group. However, after 1.1±0.3 procedures, BNP levels (335±247 to 111±95 vs. 167±107 to 90±134pg/mL) and LAVI (62±19 to 44±12 vs. 52±22 to 42±17ml/m 2 ) were significantly decreased in each (all p&lt;0.05 by paired t-test) and reached levels that were not significantly different in both groups. In addition, during 13.9±15.6 months after the first procedure, although recurrences of AF/atrial tachycardia were observed in 28 patients, the Kaplan-Meier curve analysis revealed no significant difference in recurrence-free survival between the two groups (Log-rank p=0.944, Figure). Conclusion: These data suggest that AF catheter ablation is effective even in patients diagnosed with HFpEF by a high HFA-PEFF score in terms of maintaining sinus rhythm comparable to patients with lower scores and improvements in cardiac function.
Abstract 13701: The Lumen Diameter Enlargement of the Carotid Arteries Increased the Risk of Stroke Incidence in a Japanese Urban Population: The Suita Study
Authors: Masayuki Teramoto, Yoshihiro Kokubo, Ahmed Arafa, Rena Kashima, Keiko Shimamoto, Hiroharu Kataoka, Koji Iihara
Journal: Circulation (2022)

Introduction: We aimed to examine the impact of increased LD of common carotid arteries (CCA), external carotid arteries (ECA), and internal carotid arteries (ICA) on the risk of incident stroke in a general population. Methods: We studied 3,356 Japanese men and women without cardiovascular disease whose CCA, ECA, and ICA were measured by carotid ultrasonography on both sides at baseline (October 2001 to March 2005). We confirmed the near and far walls intima-media interfaces by Doppler and calculated the lumen diameter as the distance between the intima-to-lumen interface of the near-wall to the lumen-to-intima interface of the far wall. The Cox proportional hazard model was used to calculate the multivariable-adjusted hazard ratios (HRs) with 95% conﬁdence intervals (CIs) of stroke incidence according to the CCA, ECA, and ICA LD. Results: During 30,818 person-years of follow-up, we observed 105 incident stroke cases. The higher CCA and ECA LD were associated with increased risks of incident stroke. The associations were attenuated by additional adjustment for blood pressure levels and antihypertensive drugs use, but remained statistically significant. Further adjustment of other traditional cardiovascular risk factors and carotid plaque did not alter the association materially; the multivariable-adjusted HR per standard deviation increase of CCA LD was 1.30 (95% CI, 1.05 to 1.61). Compared with participants in the first quartile (&lt; 4.8 mm) of ECA LD, the multivariable-adjusted HRs of incident stroke were 1.71 (95% CI, 0.86 to 3.38) for those in the second quartile (4.8 - 5.3 mm), 2.18 (95% CI, 1.13 to 4.23) for the third quartile (5.4 - 6.0 mm), and 1.62 (95% CI, 0.79 to 3.29) for the fourth quartile (≥ 6.0 mm) of ECA LD. Such associations were not observed for ICA LD. Conclusions: In addition to the traditional risk factors and carotid plaque, CCA and ECA LD can improve risk reclassification of incident stroke in a general urban population.
Abstract 13653: Leveraging Natural Language Processing and Machine Learning to Predict Worsening Heart Failure Events
Authors: Rishi V Parikh, Andrew P Ambrosy, Thida Tan, Sue Hee Sung, Ankeet Bhatt, Jesse K Fitzpatrick, Kent Y Feng, Keane Lee, Sirtaz Adatya, Dana R Sax, Xian Shen, Joaquim Cristino, Alan S Go
Journal: Circulation (2022)

Background: Prior risk models in patients with heart failure (HF) have focused on hospitalizations for worsening HF (WHF) and have not evaluated for differences in predictors by left ventricular ejection fraction (LVEF). We used natural language processing (NLP) and machine learning methods with access to longitudinal electronic health record (EHR) data to develop risk prediction models for WHF events across practice settings and by LVEF category. Methods: We identified all adults with HF and known LVEF on January 1 st of each year from 2011-2019 in an integrated health care system. WHF events within 1 year were defined as any hospitalization, emergency department, or outpatient encounter with ≥1 symptom, ≥2 objective findings including ≥1 sign, and ≥1 change in HF-related therapy. Signs and symptoms were ascertained using rule-based NLP. We conducted boosted decision tree-based ensemble models for any WHF event within each LVEF category: HF with reduced EF (HFrEF; LVEF ≤40%), HF with mildly reduced EF (HFmrEF; LVEF 41-49%), and HF with preserved EF (HFpEF; LVEF ≥50%). We evaluated model discrimination using area under the curve (AUC) and model calibration using Brier scores. Results: Among 359,298 patients from 2011-2019, 65,838 (18%) had HFrEF, 52,491 (15%) had HFmrEF, and 240,969 (67%) had HFpEF. Mean age was 75±12, 47% were women, and 37% were minorities including 10% Black, 11% Asian/Pacific Islander, and 12% of Hispanic ethnicity. WHF events occurred in 22% of patients with HFrEF, 17% with HFmrEF, and 16% with HFpEF. The models displayed an AUC of 0.75 and Brier score of 0.15 for HFrEF and an AUC of 0.77 and Brier scores of 0.12 for both HFmrEF and HFpEF. Clinical predictors were similar across LVEF categories ( Table ). Conclusions: Longitudinal EHR data can be leveraged using NLP and machine learning for accurate risk estimation that reliably identifies clinical predictors across a range of LVEF. These findings may provide novel insight into the natural history of HF.
Abstract 14473: The Impact of Dietary Patterns on Cardiovascular Death Comparing Populations of United States and Great Britain: An Analysis of the Global Burden of Disease Study 2019
Authors: Anoop Titus, Anu Saji, Pramukh Arun Kumar, Mahati Dasari, FNU Avinashsingh Eswarsingh, Abiram Baburaj, Akil A Sherif, yasar sattar, Rohan Mathews Koshy, Pramod Gaikwad, Michelle hadley
Journal: Circulation (2022)

Introduction: Dietary risk factors contribute to cardiovascular mortality. To the best of our knowledge, there are no studies comparing two first world countries with respect to cardiovascular deaths (CVD) and the impact of dietary risk factors. We sought to compare these parameters in Great Britain (GBR) and the United States of America (USA) Methods: A total of 33,041,416 patients with dietary risk factors and CVD from GBR and USA was obtained from the Global Burden of Disease Study between 1990 and 2016.The 30-year mean CVD was compared for all risk factors with the Welch Two sample t-test. Trends of CVD proportions of 30-years is as shown (Fig 1 and 2). Results: 30-year mean cardiovascular death for all variables between GBR and USA was statistically significant (p&lt; 0.05) with the exception of diet low in whole grains. Cardiovascular death with risk factors of diet low in PUFA, fruits, vegetable, nuts and seeds were measures where GBR had a higher 30-year mean CVD than the USA. Remaining factors contributed to higher CVD proportion in USA. Conclusions: A higher proportion of CVD was seen in the USA with dietary risk factors including low PUFA, processed meat, sweetened beverages, low legumes, high sodium and high trans-fatty acids when compared to GBR. Our study proves that there exists significant disparity in CVD proportions between two first world countries despite similar dietary risk factors.
Abstract 13304: Sox17 Deficiency Induces Pulmonary Hypertension Through E2F1/BRD4 Signaling
Authors: Dan Yi, Bin Liu, Karina Ramirez, Rebecca Li, Jiakai Pan, Won Hee Lee, Mrinalini Kala, Michael B. Fallon, Zhiyu Dai
Journal: Circulation (2022)

Introduction: Pulmonary arterial hypertension (PAH) is a disaster disease characterized by obliterative vascular remodeling and persistent increase of vascular resistance, leading to right heart failure and premature death. Understanding the cellular and molecular mechanisms will help develop novel therapeutic approaches for PAH patients. Hypothesis: Genetic SOX17 mutations are associated with PAH. We hypothesized that endothelial SOX17 mutations or loss of function contributes to endothelial dysfunction and the pathogenesis of PAH. Methods: Endothelial-specific deletion of Sox17 ( Sox17iCKO ) mice were generated. Sox17iCKO and Sox17f/f (WT) mice after tamoxifen injection were incubated without or with hypoxia (10% O 2 ) for 3 weeks to induce PH. EC proliferation, apoptosis, cell junction assay, Western blotting, QRT-PCR, RNA-sequencing analysis, and luciferase assays were performed to understand the molecular mechanisms of SOX17 deficiency and mutation in ECs. siRNA and inhibitors were used to determine the involvement of E2F1/BRD4 signaling in SOX17 deficiency ECs. Results: Sox17iCKO mice developed spontaneous mild PH and exaggerated hypoxia-induced PH evidenced by the increase of RVSP and RV hypertrophy compared to WT mice. SOX17 knockdown in human PVECs induced cell proliferation, anti-apoptosis, and impaired cell integrity. SOX17 knockdown reduced BMPR2 signaling. SOX17 knockdown and mutations at the HMG domain lost transcriptional activities and its ability to repress -catenin. RNA-seq analysis demonstrated enrichment of cell cycle pathway after the loss of SOX17 in PVECs. iRegulon analysis revealed the involvement of transcriptional factor E2F1. siRNA-mediated E2F1 knockdown normalized SOX17 deficiency-induced PVECs dysfunction. Knockdown SOX17 significantly upregulated E2F1 promoter activity, which was dependent on the binding site in the E2F1 promoter by luciferase and mutagenesis assay. E2F1 or BRD4 inhibitors attenuated SOX17 deficiency-induced PH in mice. Conclusions: Our study demonstrated that endothelial loss of SOX17 induces PH in mice. Pharmacological inhibition of E2F1/BRD4 signaling attenuated PH development in Sox17iCKO mice.
Abstract 14476: Automatic Radiomics-Based Assessment of Myocardial Texture in Transthyretin Cardiac Amyloidosis: A 2D Echocardiographic Study
Authors: Yesh Datar, Sarah Cuddy, Gavin Ovsak, Sunil Saith, Gerard Giblin, Camden Bay, Mathew S Maurer, Frederick Ruberg, Rodney H Falk, Rima Arnaout, Sharmila Dorbala
Journal: Circulation (2022)

Introduction: Myocardial i nfiltration with amyloid fibrils increases myocardial echogenicity on echocardiography (echo). Increased echogenicity has been challenging to quantify. Radiomics methods may better detect changes in echogenicity than the human eye. Our objectives were (1) to detect an altered myocardial echogenicity in transthyretin cardiac amyloidosis (ATTR-CM) using radiomics analysis and (2) to compare myocardial echogenicity by radiomics to human interpretation. Methods: We evaluated echo images of 515 patients with suspected ATTR-CM referred for an 99m-technetium pyrophosphate scan at 3 major amyloidosis centers. Myocardial echogenicity was assessed at the basal interventricular septum using an open-source radiomics platform (LIFEx) to extract 41 texture-based features. The texture features were processed using a cloud platform (BigML), which performed automated model selection and hyperparameter tuning (Figure). The studies were randomly split into training (80%) and evaluation (20%) sets. Two echo and amyloidosis experts visually evaluated myocardial echogencity on 80 random studies and classified them into ATTR-CM or non- ATTR-CM. Results: In this cohort, 57% of patients were diagnosed with ATTR-CM. The best radiomics model was a decision forest with bootstrapping, with an AUC of 0.79 (95% CI: 0.70-0.88) for diagnosing ATTR-CM. By contrast, visual classification of echo texture as ATTR-CM or not was poor; the interobserver agreement for assessing a septal ROI for altered myocardial echogenicity consistent with ATTR-CM was a kappa of 0.29 and using the entire apical 4 chamber view 0.44. Given the poor agreement an AUC could not be calculated. Conclusions: We have validated the use of a radiomics approach to evaluate myocardial echogenicity in ATTR-CMP. This work lays the foundation to evaluate changes in myocardial texture using echo to raise the suspicion of cardiac amyloidosis and assess changes following targeted TTR therapies.
Abstract 13781: Same-Day Discharge After Transcatheter Mitral Valve Repair: Propensity Score-Matched Analysis From the Nationwide Readmissions Database 2014-2019
Authors: Akshay Goel, Aaqib H Malik, Dhrubajyoti Bandyopadhyay, Rahul Gupta, Adrija Hajra, Wilbert S Aronow, HASAN AHMAD
Journal: Circulation (2022)

Introduction: Transcatheter mitral valve repair (TMVR) has evolved over the years, and early discharge strategies are being increasingly adopted. However, there is paucity of data on the outcomes and safety of same-day discharge (SDD) after TMVR. Methods: Data from the Nationwide Readmissions Database 2014 to 2019 were analyzed. International Classification of Diseases codes were used to identify adult patients admitted for elective TMVR. Patients who underwent uncomplicated TMVR were identified by excluding patients with periprocedural complications such as bleeding, vascular access site complications, pericardial complications, stroke, myocardial infarction, shock, or death before discharge. A 1:3 propensity score-matched analysis was performed to compare outcomes of patients undergoing SDD and different-day discharge (DDD). The primary outcome of interest was the 30-day unplanned readmission rate. Results: We identified 34,683 patients who received complication-free TMVR, of which 232 (0.67%) underwent SDD. There was a gradually rising trend of SDD after TMVR over the study period. The baseline characteristics of the unmatched and propensity-matched SDD and DDD groups are shown. Patients in SDD group did not have a significantly higher 30-day readmission rate (15.7% vs 14.8%, p = 0.82) compared to DDD group, but had significantly lower mean hospitalization costs ($33,060 vs $41,134, p &lt;0.001). Female gender, diabetes, chronic kidney or pulmonary disease, anemia, liver disease, cancer and atrial fibrillation were found to be independent predictors of 30-day readmissions after TMVR (shown in figure). Conclusions: Patients receiving a complication-free TMVR who were discharged on the same day as the procedure had a similar 30-day unplanned readmission rate compared with those that stayed in the hospital longer. Our findings suggest that same-day discharge after uncomplicated TMVR may be a safe and cost-effective strategy in selected patients.
Abstract 13274: The Safety of Early Discharge After Tavi in Northern and Rural Ontario Canada
Authors: George Hanna, Derek MacDonald, Bindu Bittira, Eric Horlick, Noman Ali, Rony Atoui, Neil Fam, Mohammed Shurrab, Joanne Spadafore, Julie Allen, Asim Cheema, Bhanu Nalla, Carly Pulkkinen, Sylvain Cote, Hooman Hennessey, Melissa Stringer, Joanne Collin, John Fenton, Sandra Lauck, Janarthanan Sathananthan, DAVID WOOD, Sami Al-Nasser
Journal: Circulation (2022)

Introduction: Early hospital (&lt;48hrs) discharge following transcatheter aortic valve implantation (TAVI) is an increasingly adopted practice. However, the safety of such an approach among patients residing in rural areas in Northern Ontario, including remote and medically underserved areas is lacking. Methods: After adapting the Vancouver 3M clinical pathway, all patients who underwent TAVI in Sudbury, Ontario were included in the analysis. The primary endpoint was all-cause mortality within 30 days. Secondary endpoints included procedural complications, post-TAVI length of hospital stay (LOS) and 30-day re-hospitalizations. Results: 165 patients underwent TAVI after adapting the Vancouver 3M clinical pathway. Mean age was 81 years (SD ± 8). Median STS-mortality score was 2.5% (IQR, 1.9-3.5). There was one in-hospital death (0.6%) with no 30 day mortality observed beyond hospital discharge. 11 patients (6.7%) required rehospitalization within 30 days, 3 of them for cardiac complaints. More over, after adoption of the 3M clinical pathway, the need for procedural mechanical ventilation and surgical vascular cut-down declined from 100% and 97% at baseline, to 6% and 2% respectively. Similarly, after adapting the 3M clinical pathway, the number of patients receiving TAVI on a given procedural day increased from two to three patients. Median post TAVI-LOS declined from 5 days (2-6 days) to 1 day (1-3 days). Conclusions: By transitioning to a 3M approach, our study has shown that early discharge after TAVI in Northern Ontario at a single lower-volume TAVI centre is feasible and safe, with favorable outcomes and improved hospital LOS. Furthermore, resource utilization improved with fewer patients requiring mechanical ventilation and surgical cut-down, leading to a downstream increase in the number of patients receiving TAVI on a given procedural day. This experience can potentially improve TAVI equity for underserved and vulnerable populations, reduce TAVI wait times and bridge variations in TAVI funding.